This is an application for a Mentored Patient-Oriented Research Career Development Award. The goal of the proposed project is to provide the candidate with advanced skills needed to establish an independent program of migraine research evaluating the factors that influence the generation and progression of migraine and how to improve migraine treatment. To facilitate this long-term career goal the candidate will examine the impact of co-morbid conditions, particularly obesity, on migraine onset and severity, as well as potential mechanisms for this association. The candidate proposes a comprehensive training plan, combining didactic instruction overseen by her mentors, formal coursework, participation in applied training experiences with individual advisors, and participation in seminars and workshops. Specific training goals include: (1) advance training in clinical pain research, (2) training in the methodologies of molecular proteomics, (3) training in body composition assessment, (4) training in biostatistics, (5) training in neuroepidemiology, and (6) training in the responsible conduct of research. The training plan will be executed in coordination with a proposed set of research studies that are based upon preliminary data collected by the candidate, demonstrating an epidemiological association between migraine and obesity in individuals of reproductive age as well as the differential expression of inflammatory-related adipokines (proteins secreted primarily from adipocytes in adipose tissue) in those with chronic migraine vs. those with episodic migraine or controls. The proposed research will build upon these preliminary findings by studying adipokine expression and body composition using dual energy x-ray absorptiometry and abdominal MRI imaging in a clinical cohort of obese and nonobese migraineurs as compared to controls. Additionally, data from a community-based epidemiological study will also be used to examine factors related to the development of new onset migraine in obese participants. The proposed application will therefore further define the migraine-obesity association, identify potential neurobiological mechanisms for the association of migraine with obesity and identify potential novel treatment targets for migraine. PUBLIC HEALTH RELEVANCE: The aim of this study is to examine the impact and mechanisms of disorders which commonly co-occur in those with migraine headaches (such as obesity); and specifically how these conditions impact the onset and progression of migraine headaches over time. The importance of this research to public health is that results may identify new ways of reducing the frequency of migraines or improving treatment.